rs12535996

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000245.4(MET):​c.-15+12518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,132 control chromosomes in the GnomAD database, including 2,148 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 2148 hom., cov: 32)

Consequence

MET
NM_000245.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
MET (HGNC:7029): (MET proto-oncogene, receptor tyrosine kinase) This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
METNM_000245.4 linkuse as main transcriptc.-15+12518G>A intron_variant ENST00000397752.8
COMETTNR_165032.1 linkuse as main transcriptn.87+2846C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
METENST00000397752.8 linkuse as main transcriptc.-15+12518G>A intron_variant 1 NM_000245.4 P3P08581-1

Frequencies

GnomAD3 genomes
AF:
0.128
AC:
19389
AN:
152014
Hom.:
2129
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.303
Gnomad AMI
AF:
0.0746
Gnomad AMR
AF:
0.0833
Gnomad ASJ
AF:
0.0274
Gnomad EAS
AF:
0.0191
Gnomad SAS
AF:
0.0726
Gnomad FIN
AF:
0.0538
Gnomad MID
AF:
0.0981
Gnomad NFE
AF:
0.0612
Gnomad OTH
AF:
0.111
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.128
AC:
19446
AN:
152132
Hom.:
2148
Cov.:
32
AF XY:
0.124
AC XY:
9220
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.303
Gnomad4 AMR
AF:
0.0833
Gnomad4 ASJ
AF:
0.0274
Gnomad4 EAS
AF:
0.0189
Gnomad4 SAS
AF:
0.0724
Gnomad4 FIN
AF:
0.0538
Gnomad4 NFE
AF:
0.0612
Gnomad4 OTH
AF:
0.111
Alfa
AF:
0.103
Hom.:
227
Bravo
AF:
0.138
Asia WGS
AF:
0.0850
AC:
296
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.063
DANN
Benign
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12535996; hg19: chr7-116325149; API